Role of cotranslational folding for β-sheet-enriched proteins: A perspective from molecular dynamics simulations

The formations of correct three-dimensional structures of proteins are essential to their functions. Cotranslational folding is vital for proteins to form correct structures in vivo. Although some experiments have shown that cotranslational folding can improve the efficiency of folding, its microscopic mechanism is not yet clear. Previously, we built a model of the ribosomal exit tunnel and investigated the cotranslational folding of a three-helix protein by using all-atom molecular dynamics simulations. Here we study the cotranslational folding of three \ensuremath{\beta}-sheet-enriched proteins using the same method. The results show that cotranslational folding can enhance the helical population in most cases and reduce non-native long-range contacts before emerging from the ribosomal exit tunnel. After exiting the tunnel, all proteins fall into local minimal states and the structural ensembles of cotranslational folding show more helical conformations than those of free folding. In particular, for one of the three proteins, the GTT WW domain, we find that one local minimum state of the cotranslational folding is the known folding intermediate, which is not found in free folding. This result suggests that the cotranslational folding may increase the folding efficiency by accelerating the sampling more than by avoiding the misfolded state, which is presently a mainstream viewpoint.